Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility

Valerie A. Larson, Yevgeniya Mironova, Kimberly G. Vanderpool, Ari Waisman, John E. Rash, Amit Agarwal, Dwight E. Bergles

Research output: Contribution to journalArticlepeer-review

Abstract

The inwardly rectifying K+ channel Kir 4.1 is broadly expressed by CNS glia and deficits in Kir 4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir 4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir 4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir 4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+ and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir 4.1 channels in oligodendrocytes play an important role in extracellular K+ homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+ clearance and promote seizures.

Original languageEnglish (US)
Article numbere34829
JournaleLife
Volume7
DOIs
StatePublished - Mar 29 2018

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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